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Oxidative Medicine and Cellular Longevity
Volume 2014 (2014), Article ID 485604, 9 pages
Research Article

Lipoxygenase Pathway Mediates Increases of Airway Resistance and Lung Inflation Induced by Exposure to Nanotitanium Dioxide in Rats

1Department of Nursing, St. Mary’s Medicine Nursing and Management College, Yilan County 266, Taiwan
2Department of Emergency and Critical Care, Cheng-Hsin General Hospital, Taipei 112, Taiwan
3Department of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan
4Division of Chest Medicine, Department of Internal Medicine, Shin Kong Wu-Ho-Su Memorial Hospital, Taipei 11101, Taiwan
5Division of Thoracic Surgery, Department of Surgery, Chi-Mei Foundation Medical Center, Tainan 71004, Taiwan
6Department of Pathology, Cardinal Tien Hospital, New Taipei City 23148, Taiwan

Received 13 October 2013; Revised 12 December 2013; Accepted 16 December 2013; Published 17 February 2014

Academic Editor: Felipe Dal-Pizzol

Copyright © 2014 Jyu-Feng Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Nanotitanium dioxide particle (nTiO2) inhalation has been reported to induce lung parenchymal injury. After inhalation of nTiO2, we monitored changes in 5-lipoxygenase, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) mRNA in rat lung tissue. Lung function parameters include specific airway resistance (SRaw), peak expiratory flow rate (PEF), functional residual capacity (FRC), and lung compliance (Cchord); blood white blood cell count (WBC), nitric oxide (NO), hydrogen peroxide, and lactic dehydrogenase (LDH); and lung lavage leukotriene C4, interleukin 6 (IL6), tumor necrotic factor α (TNFα), hydroxyl radicals, and NO. Leukotriene receptor antagonist MK571 and 5-lipoxygenase inhibitor MK886 were used for pharmacologic intervention. Compared to control, nTiO2 exposure induced near 5-fold increase in 5-lipoxygenase mRNA expression in lung tissue. iNOS mRNA increased while eNOS mRNA decreased. Lavage leukotriene C4; IL6; TNFα; NO; hydroxyl radicals; and blood WBC, NO, hydrogen peroxide, and LDH levels rose. Obstructive ventilatory insufficiency was observed. MK571 and MK886 both attenuated the systemic inflammation and lung function changes. We conclude that inhaled nTiO2 induces systemic inflammation, cytokine release, and oxidative and nitrosative stress in the lung. The lipoxygenase pathway products, mediated by oxygen radicals and WBC, play a critical role in the obstructive ventilatory insufficiency induced by nTiO2.